Cervical Cancer

Key Points

HPV Testing in Women

Diagnosis

Indications for Testing

Laboratory Testing

  • Refer to Key Points section in HPV topic

Monitoring

  • HPV molecular testing, in conjunction with cytology, aids in monitoring women for recurrent disease post treatment for CIN2 or more severe grade
  • Refer to ASCCP consensus guidelines

Clinical Background

Carcinoma of the cervix is a common cause of cancer in women worldwide, but has decreased in prominence in the U.S. with advances in screening.

Epidemiology

  • Prevalence – >12,000 new cases in the U.S. in 2014 (NCCN, 2015)
    • Third most common cancer in women worldwide
  • Age – median is 48 years
    • Infection with oncogenic strain of human papillomavirus (HPV) associated with earlier age of onset
      • High-grade dysplasia in 30s
      • Invasive carcinoma in 40s

Risk Factors

  • Sexual activity
    • Infection with oncogenic (high-risk) types of HPV 
    • History of early sexual activity, especially with multiple sex partners
    • Sexual partner who began sexual activity at an early age or who had many previous sexual partners
    • History of sexually transmitted infections (STIs)
  • Family history of cervical cancer
  • Previous diagnosis of dysplasia on a Pap test or prior gynecological malignancy
  • Tobacco use
  • Exposure to diethylstilbestrol (DES) before birth
  • HIV infection
  • Weakened immune system (eg, organ transplant, chemotherapy, chronic corticosteroid use)

Pathophysiology

  • Etiology – HPV, particularly the oncogenic types
    • HPV 16 and 18 are responsible for >70% of invasive cervical cancers
  • Tumor types – 80% are squamous cell carcinoma, 20% are adenocarcinomas
    • Increased incidence of adenocarcinomas over last 30 years
      • Cytologic screening methods are less effective for adenocarcinomas, but HPV testing may improve detection rates
  • Usually evolves from cervical dysplasia
    • 30-35% of high-grade dysplasias progress to invasive carcinoma

Clinical Presentation

  • Earliest stage may be asymptomatic or have watery vaginal discharge
  • Abnormal vaginal bleeding or a significant unexplained change in menstrual cycle
  • A friable cervix that bleeds easily following intercourse or contact (eg, insertion of a diaphragm, collection of a Pap smear)
  • Pain during sexual intercourse
  • Abnormal vaginal discharge containing blood-tinged mucous

Treatment

Prevention

  • HPV vaccine – recommended for males and females 9-26 years of age in 3 doses

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Cytology, ThinPrep Pap Test and Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) (for routine co-testing in women over 30) 2000136
Method: Microscopy/Qualitative Transcription-mediated Amplification

Preferred FDA-approved test for 5-year interval testing (co-testing) in women ≥30 years

Triage women with equivocal and mildly abnormal cervical cytology

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940
Method: Qualitative Polymerase Chain Reaction

FDA-approved platform for primary HPV screening in women ≥25 years

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

Follow-up test for abnormal cytology results in women ≥30 years

Test amplifies DNA of HPV16, HPV18 and 12 high-risk HPV types associated with cervical cancer and its precursor lesions (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA) with Reflex to HPV Genotypes 16 and 18/45 by TMA, ThinPrep 2007890
Method: Qualitative Transcription-Mediated Amplification

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years; genotyping performed for triaging women to colposcopy who are cytology-negative (NILM) and HPV-positive

 

Refer to Key Points section in HPV topic

Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2000138
Method: Microscopy/Qualitative Transcription-mediated Amplification

Preferred FDA-approved test for routine cervical cancer screening in women 21-<25 years

An option for 3-year cervical cancer screening intervals in women 25-65 years

For preferred co-testing panel, refer to Cytology, ThinPrep Pap test and hrHPV by TMA    

 

Refer to Key Points section in HPV topic

Cytology, SurePath Liquid-Based Pap Test 2000134
Method: Microscopy

May be used for routine 3-year interval cervical cancer screening test in all women

For 5-year interval testing (co-test) in women 30-65 years, order with HPV test (hrHPV PCR, SurePath; or HPV 16 and 18 genotype PCR, SurePath)

 

Refer to Key Points section in HPV topic

Cytology, ThinPrep® Pap Test 2000137
Method: ThinPrep® 2000 System/Routine Cytopathologic Evaluation

May be used for routine 3-year interval cervical cancer screening test in all women ≥21 years

For 5-year interval testing (co-test) in women 30-65 years, order with HPV ThinPrep test (hrHPV PCR, ThinPrep; or hrHPV by TMA, ThinPrep)

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep 2007893
Method: Qualitative Transcription-Mediated Amplification

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

Follow-up test for abnormal cytology results in women ≥21 years

Detects E6/E7 viral messenger RNA of the high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 associated with cervical cancer and its precursor lesions

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947
Method: Qualitative Polymerase Chain Reaction

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years

Follow-up test for abnormal cytology results in women ≥21 years

Follow up ASC-US cytology in women ≥30

Does not include reflex to genotype

Test amplifies DNA of 14 high-risk HPV types associated with cervical cancer and its precursor lesions (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV) Genotypes 16 and 18/45 by Transcription-Mediated Amplification (TMA), ThinPrep 2007894
Method: Qualitative Transcription-Mediated Amplification

FDA-approved test for triaging women ≥30 years with negative cervical cytology (NILM Pap smear) and positive HPV test

Detects E6/E7 viral messenger RNA of the high-risk HPV types 16, 18, and 45 only

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, SurePath 2011933
Method: Qualitative Polymerase Chain Reaction

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep test (hrHPV 16 and 18 genotype PCR, ThinPrep)

Test amplifies DNA of HPV16, HPV18 and 12 other high-risk HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) associated with cervical cancer and its precursor lesions

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV), High Risk by PCR, SurePath 2011942
Method: Qualitative Polymerase Chain Reaction

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep testing (hrHPV TMA, ThinPrep; or hrHPV PCR, ThinPrep)

 

Refer to Key Points section in HPV topic

Human Papillomavirus (HPV) 16 and 18 Genotype by PCR, SurePath 2011937
Method: Qualitative Polymerase Chain Reaction

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended.

Refer to corresponding ThinPrep testing (hrHPV 16 and 18 genotype PCR, ThinPrep)

Test amplifies DNA of HPV 16 and HPV 18

 

Refer to Key Points section in HPV topic

Cytology, SurePath Liquid-Based Pap Test and Human Papillomavirus (HPV), High Risk by Hybrid Capture (for routine co-testing in women over 30) 2000133
Method: Microscopy/Qualitative Nucleic Acid Probe

For HPV testing, only FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep testing (Cytology ThinPrep Pap test and HPV by TMA)

 

Refer to Key Points section in HPV topic

Squamous Cell Carcinoma Antigen, Serum 0081054
Method: Quantitative Enzyme-Linked Immunosorbent Assay

May be helpful in monitoring for recurrent disease

Results obtained with different assay methods or kits cannot be used interchangeably

SCC antigen levels alone should not be interpreted as evidence of the presence or absence of malignant disease

In patients with known or expected cancer, other tests and procedures must be considered for diagnosis and patient management

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Cytology, Pap Smear 2000624
Method: Microscopy

Use for screening and detection of cervical cancer

Human Papillomavirus (HPV), High Risk by in situ Hybridization, Paraffin 2002899
Method: In situ Hybridization

Preferred in situ hybridization test to detect high-risk HPV subtypes (16, 18) in formalin-fixed, paraffin-embedded tissue

Human Papillomavirus (HPV) Low Risk by in situ Hybridization, Paraffin 2002896
Method: In situ Hybridization

Preferred test is HPV high-risk in situ hybridization if determining potential cancer risk

Human Papillomavirus (HPV), High Risk by Hybrid Capture, ThinPrep 2008404
Method: Qualitative Nucleic Acid Probe

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

Follow-up test for abnormal cytology results in women ≥21 years

Detects high-risk HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 associated with cervical cancer and its precursor lesions

Human Papillomavirus (HPV), High Risk by Hybrid Capture, Cervical Brush 0065999
Method: Qualitative Nucleic Acid Probe

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

Follow-up test for abnormal cytology results in women ≥21 years

Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by Hybrid Capture 2000135
Method: Microscopy/Qualitative Nucleic Acid Probe

For HPV testing, only FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep testing (Cytology ThinPrep Pap test with reflex to HPV by TMA)

Human Papillomavirus (HPV), High Risk by Hybrid Capture, SurePath 0060744
Method: Qualitative Nucleic Acid Probe

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended

Refer to corresponding ThinPrep testing (hrHPV TMA, ThinPrep; or hrHPV PCR, ThinPrep)